Weight change in older adults and mortality: the Multiethnic Cohort Study.

OBJECTIVE: To investigate the association between weight change in older adults and mortality in a multiethnic population. METHODS: We performed a prospective analysis using data on weight change between the baseline (1993-1996) and the 10-year follow-up (2003-2007) surveys in relation to subsequent mortality among 63 040 participants in the Multiethnic Cohort Study in Hawaii and California. The participants were African American, Native Hawaiian, Japanese American, Latino and white, aged 45-75 years at baseline, and did not report heart disease or cancer at either survey. RESULTS: During an average of 7.3 years of follow-up after the 10-year survey, 6623 deaths were identified. Compared with individuals whose weight remained stable (±2.5 kg), those who lost weight and those with the highest weight gain (>10 kg) were at increased risk of all-cause mortality, with the risks greater for the weight loss (hazard ratios (HR): 2.86; 95% confidence interval (95% CI): 2.62-3.11 for >10 kg) than the weight-gain group (HR: 1.25; 95% CI: 1.11-1.41 for >10 kg), thus resulting in a reverse J-shaped curve. Japanese Americans and Latinos had stronger associations of weight loss >10 kg with mortality than did African Americans, Native Hawaiians and whites. The increase in risk with weight gain >10 kg was greater for older (⩾55 years at baseline) than younger individuals, whereas the increase in mortality associated with weight loss was greater for the normal weight (<25 kg m-2 at baseline) participants and never smokers, compared with overweight/obese persons and current smokers, respectively. CONCLUSIONS: Our findings confirm the association between weight change and a higher mortality in a healthy, multiethnic population, with higher risks for weight loss than weight gain. On the basis of these observations, public health recommendation should focus on the prevention of weight loss, as well as weight stability within the non-obese range, for middle-aged and older adults.

Ethnic differences in serum adipokine and C-reactive protein levels: the multiethnic cohort.

BACKGROUND: Ethnic disparities in metabolic disease risk may be the result of differences in circulating adipokines and inflammatory markers related to ethnic variations in obesity and body fat distribution. SUBJECTS/METHODS: In a cross-sectional design, we compared serum levels of leptin, adiponectin, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in control subjects (321 men and 930 women) from two nested case-control studies conducted within the Multiethnic Cohort Study consisting of whites, Japanese Americans (JA), Latinos, African Americans (AA) and Native Hawaiians (NH). General linear models were applied to evaluate ethnic differences in log-transformed serum biomarker levels before and after adjusting for body mass index (BMI) at cohort entry. RESULTS: In comparison to whites, significant ethnic differences were observed for all biomarkers except TNF-α. JA men and women had significantly lower leptin and CRP levels than whites, and JA women also had lower adiponectin levels. Leptin was significantly higher in AA women (P < 0.01), adiponectin was significantly lower in AA men and women (P = 0.02 and P < 0.001), and CRP and IL-6 were significantly higher in AA men and women. Lower adiponectin (P < 0.0001) and CRP (P = 0.03) levels were the only biomarkers in NH women that differed from whites; no statistically significant differences were seen for NH men and for Latino men and women. When adjusted for BMI at cohort entry, the differences between the lowest and the highest values across ethnic groups decreased for all biomarkers except adiponectin in men indicating that ethnic differences were partially due to weight status. CONCLUSIONS: These findings demonstrate the ethnic variations in circulating adipokine and CRP levels before and after adjustment for BMI. Given the limitation of BMI as a general measure of obesity, further investigation with visceral and subcutaneous adiposity measures are warranted to elucidate ethnicity-related differences in adiposity in relation to disparities in obesity-related disease risk.

A candidate gene approach to searching for low-penetrance breast and prostate cancer genes.

Most cases of breast and prostate cancer are not associated with mutations in known high-penetrance genes, indicating the involvement of multiple low-penetrance risk alleles. Studies that have attempted to identify these genes have met with limited success. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium--a pooled analysis of multiple large cohort studies with a total of more than 5,000 cases of breast cancer and 8,000 cases of prostate cancer--was therefore initiated. The goal of this consortium is to characterize variations in approximately 50 genes that mediate two pathways that are associated with these cancers--the steroid-hormone metabolism pathway and the insulin-like growth factor signalling pathway--and to associate these variations with cancer risk.

Adherence to recommendations for fruit and vegetable intake, ethnicity and ischemic heart disease mortality.

BACKGROUND AND AIMS: Ischemic heart disease (IHD) accounts for one-third of annual deaths in the U.S. and mortality rates vary by ethnicity. The association between adherence to dietary guidelines for fruit and vegetable intake with IHD mortality among different ethnic groups has not previously been examined. METHODS AND RESULTS: A prospective cohort design was used to examine the incidence of fatal IHD among participants in the Multiethnic Cohort Study. Participants included 164,617 men and women from five ethnic groups: African American, Native Hawaiian, Japanese American, Latino, and Caucasian. Cox proportional hazards models, stratified by ethnicity and sex, were used to examine associations between adherence with recommended dietary guidelines for fruit and vegetable intake and risk for fatal IHD. The results did not provide evidence that the association between adherence with dietary recommendations for fruit or vegetable intake and IHD mortality varies by ethnicity. Pooled data did provide evidence that adhering to the recommendations for vegetables lowered risk among men (RR = 0.84, 95% CI: 0.74-0.96) and women (RR = 0.80, 95% CI: 0.69-0.94). No significant effects were observed for fruit intake. CONCLUSIONS: The effect of dietary intake of fruit and vegetables did not vary by ethnicity, providing evidence that recommendations do not need to be individualized for these special populations. The protective effect observed for vegetable intake among both sexes confirms previous findings and supports the evidence base for promoting diet modification in this direction.

Contribution of meat to vitamin B12, iron and zinc intakes in five ethnic groups in the USA: implications for developing food-based dietary guidelines.

BACKGROUND: To describe the sources of meat and their contributions to vitamin B12, iron and zinc in five ethnic groups in the USA. METHODS: Dietary data for the Multiethnic Cohort, established in Hawaii and Los Angeles, were collected using a quantitative food frequency questionnaire from more than 215,000 subjects, aged 45-75 years at baseline (1993-1996). Participants included African American, Latino, Japanese American, Native Hawaiian and Caucasian men and women. Servings of meat items were calculated based on the US Department of Agriculture recommendations and their contributions to intakes of total meat, red meat, vitamin B12, iron and zinc were determined. RESULTS: Of all types of meat, poultry contributed the most to meat consumption, followed by red meat and fish among all ethnicities, except for Latino (born in Mexico and Central/South America) men who consumed more beef. Lean beef was the most commonly consumed red meat for all ethnic-sex groups (9.3-14.3%), except for Native Hawaiian and Japanese American men, and Japanese American women whose top contributor was stew/curry with beef/lamb and stir-fried beef/pork with vegetables, respectively. The contribution of meat was most substantial for zinc (11.1-29.3%) and vitamin B12 (19.7-40%) and, to a lesser extent, for iron (4.3-14.2%). CONCLUSIONS: This is the first large multiethnic cohort study to describe meat sources and their contributions to selected nutrients among ethnic minorities in the USA. These findings may be used to develop ethnic-specific recommendations for meat consumption aiming to improve dietary quality among these groups.

Evidence of an X-linked or recessive genetic component to prostate cancer risk.

We used data from a population-based cohort study of blacks, Hispanics, Japanese and whites to examine the frequency of prevalent prostate and breast cancer by family history status of first-degree relatives (parents and siblings). Independent of race, the age-adjusted relative risk for prevalent prostate cancer in subjects with affected brothers was approximately two times that in subjects with affected fathers (P < 0.00005). No such excess risk for breast cancer was observed among subjects with affected sisters compared to those with affected mothers (age- and race-adjusted relative risk = 1.10, P = 0.34). The magnitude of the relative risk for prostate cancer in sibling- versus parent-affected groups was significantly different from that of the comparable relative risk for breast cancer (P < 0.00005). An excess risk of prostate cancer in men with affected brothers compared to those with affected fathers is consistent with the hypothesis of an X-linked, or recessive, model of inheritance.

Meat consumption and risk of type 2 diabetes: the Multiethnic Cohort.

OBJECTIVE: To examine the association of meat consumption with diabetes risk in the Hawaii component of the Multiethnic Cohort and to assess effect modification by ethnicity. DESIGN: A prospective cohort study. Baseline information on diet and lifestyle was assessed by questionnaire. The cohort was followed up for incident cases of diabetes, which were identified through self-reports, medication questionnaires, or health plan linkages. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals for diabetes associated with quintile of meat consumption. SETTING: Hawaii, USA. SUBJECTS: A total of 29,759 Caucasian, 35,244 Japanese-American and 10,509 Native Hawaiian men and women, aged 45-75 years at baseline. RESULTS: During a mean follow-up time of 14 years, 8587 incident diabetes cases were identified. Intake of red meat was positively associated with diabetes risk in men (fifth v. first quintile: HR=1.43; 95% CI 1.29, 1.59) and women (fifth v. first quintile: HR=1.30; 95% CI 1.17, 1.45) in adjusted models. The respective HR for processed red meat intake were 1.57 (95% CI 1.42, 1.75) and 1.45 (95% CI 1.30, 1.62). The association for processed poultry was weaker than for processed red meat, and fresh poultry intake was not associated with diabetes risk. For men only, we observed significant interactions of ethnicity with the red and processed red meat associations, with Caucasians experiencing slightly higher risks than Japanese-Americans. CONCLUSIONS: Our findings support the growing evidence that red and processed meat intake increase risk for diabetes irrespective of ethnicity and level of BMI.

The association of diabetes with colorectal cancer risk: the Multiethnic Cohort.

BACKGROUND: Diabetics have been found to have a greater risk of colorectal cancer than non-diabetics. METHODS: We examined whether this relationship differed by ethnic group, cancer site or tumour stage in a population-based prospective cohort, including 3549 incident colorectal cancer cases identified over a 13-year period (1993-2006) among 199 143 European American, African American, Native Hawaiian, Japanese American and Latino men and women in the Multiethnic Cohort. RESULTS: Diabetics overall had a significantly greater risk of colorectal cancer than did non-diabetics (relative risk (RR)=1.19, 95% confidence interval (CI)=1.09-1.29, P-value (P)<0.001). Positive associations were observed for colon cancer, cancers of both the right and left colon, and cancers diagnosed at a localised and regional/distant stage. The association with colorectal cancer risk was significantly modified by smoking status (P(Interaction)=0.0044), with the RR being higher in never smokers (RR=1.32, 95% CI=1.15-1.53, P<0.001) than past (RR=1.19, 95% CI=1.05-1.34, P=0.007) and current smokers (RR=0.90, 95% CI=0.70-1.15, P=0.40). CONCLUSION: These findings provide strong support for the hypothesis that diabetes is a risk factor for colorectal cancer.

Urinary phytoestrogen excretion and prostate cancer risk: a nested case-control study in the Multiethnic Cohort.

BACKGROUND: Phytoestrogens are of special interest in prostate cancer research because populations in Asia with a high consumption of phytoestrogens have a lower incidence of the disease than comparable populations in Western countries. METHODS: This case-control study is nested within a large multiethnic cohort in Hawaii and California. Urine samples were analysed for daidzein, genistein, equol, and enterolactone among 249 incident prostate cancer cases and 404 controls matched on age, race/ethnicity, date/time of specimen collection, and fasting status. RESULTS: The median excretion of daidzein was 0.173 nmol mg(-1) creatinine in cases and 0.291 in controls (P=0.01), and the median excretion of genistein was 0.048 in cases and 0.078 in controls (P=0.05). An inverse association was seen for daidzein overall (odds ratio for the highest vs lowest quintile=0.55, 95% confidence interval=0.31-0.98, P(trend)=0.03) and seemed to apply to localized (P(trend)=0.08) as well as advanced or high-grade cancer (P(trend)=0.09). This association was consistent across the four ethnic groups examined. Although the relationship was weaker for genistein, the odds ratios and trends were similarly inverse. Urinary excretion of equol and enterolactone was not significantly related to prostate cancer risk. CONCLUSION: Our findings suggest that high intake of isoflavones, as reflected by urinary excretion of daidzein and genistein, may be protective against prostate cancer.

Cancer patterns of four ethnic groups in Hawaii.

Cancer risks were compared in the Japanese, Chinese, Hawaiian, and Filipino populations of Hawaii with those in the U.S. white population. The analysis used standardized incidence ratio(s) (SIR), based on the U.S. white incidence rates for 1970. In general, the risks for many major cancers in the Japanese, Chinese, and Filipinos were low in relation to U.S. whites, whereas those for Hawaiians were high. However, the SIR values for the various cancer sites and types varied considerably within each ethnic group. Ethnic-specific data on smoking, drinking, and dietary habits and on sociologic and demographic factors were examined in relation to the SIR findings. Some of the results were consistent with current etiologic hypotheses, whereas others suggested areas for further epidemiologic study.

Leprosy and cancer: a retrospective cohort study in Hawaii.

We used data collected on a retrospective cohort of 1,123 leprosy patients living in Hawaii between 1940 and 1970, to test the hypotheses that patients with lepromatous leprosy, who have an impairment in their cellular immune response, would have an increased risk for cancer and that patients with tuberculoid leprosy, who are immunologically competent, would have a normal or even a reduced cancer risk from beneficial stimulation of their cellular immune system by exposure to the Mycobacterium leprae organisms. Based on the survival analysis method, the results of the study supported the predicted increase in cancer cases among the lepromatous leprosy patients (19 observed, 12.7 expected; risk ratio = 1.5) and the predicted decrease among the tuberculoid leprosy patients (14 observed, 17.8 expected; risk ratio = 0.8); in both groups, the findings were consistent across the five racial categories of the study. However, none of these differences between observed and expected cases was statistically significant at the 5% level. The study provided no support for the alternate hypothesis that chronic antigenic stimulation by the M. leprae organisms might lead to an increase in tumors of the lymphoreticular system.

Dietary fat and prostate cancer: current status.

Efforts to elucidate the causes of prostate cancer have met with little success to date. All that is known with certainty is that the incidence increases exponentially with age, varies by geography and by race or ethnicity, and is higher among men whose father or brother had the disease. Because the incidence changes in migrants and their offspring, exogenous factors certainly contribute to the risk of prostate cancer. Early epidemiologic studies implicated dietary fat as a likely causal factor for this cancer. However, scientific support for such an association has diminished in recent years as more epidemiologic evidence has accrued. Accordingly, we reviewed the relevant English language literature on this topic, including epidemiologic and animal studies, as well as current concepts regarding the involvement of fat in carcinogenesis to re-examine the fat-prostate cancer hypothesis. We conclude that dietary fat may indeed be related to prostate cancer risk, although the specific fat components that are responsible are not yet clear. Given the diverse effects of fatty acids on cellular biology and chemistry, it seems likely that the relationship is complex, involving the interplay of fat with other dietary factors, such as antioxidant vitamins and minerals, or with genetic factors that influence susceptibility. Some suggestions for further research are offered.

Relationship of ethnicity and other prognostic factors to breast cancer survival patterns in Hawaii.

The survival experience of 2,956 invasive breast carcinoma cases identified among the 5 major ethnic groups in Hawaii between 1960 and 1979 was studied. The study population consisted of 1,174 Caucasian, 972 Japanese, 458 Hawaiian, 226 Chinese, and 126 Filipino women. A multivariate analysis based on the proportional hazards regression model revealed that after simultaneous adjustment for stage of disease, age, and socioeconomic status (SES), Filipino and Hawaiian patients had significantly poorer survival than Japanese and Caucasian patients. Hawaiian women also had a significantly poorer survival than Chinese women. Survival was higher in patients between the ages of 45 and 54 years compared to those younger or older, in patients with localized tumors compared to those with more advanced tumors, and in patients with middle or high SES compared to those with the low SES. Histology and marital status were not associated with survival. The possibility that other factors such as obesity, estrogen receptor status, treatment, and nutritional and hormonal status could explain the remaining observed racial differences in breast cancer survival is discussed.

Dietary history methods for epidemiologic studies: application in a case-control study of vitamin A and lung cancer.

A dietary history method for use in a case-control study of vitamin A and lung cancer is described. The method was designed to obtain estimates of the usual frequencies and quantities of 84 major food sources of vitamin A and carotene consumed prior to symptoms of disease in cases and during the same time period in matched controls. Amounts were estimated from photographs of each item that showed three different quantities. The development of the questionnaire is described in detail, as well as the data collection and analysis. The results of the study showed that relative to those men with the highest intakes, the men who consumed less vitamin A or carotene had a higher risk for lung cancer in a general dose-response fashion. These findings were not apparent for females. Recommendations regarding dietary methodology for future studies concerning vitamin A and carotene intakes include further research on the validation and reproducibility of the dietary methods, identification of appropriate biological markers that reflect past exposures of vitamin A and carotene, and further research on the vitamin A and carotene content of available food items.

Application of a job-exposure matrix to a case-control study of lung cancer.

Interview information was obtained on primary and secondary occupations for 261 male lung cancer patients and 444 controls residing on the island of Oahu, HI. With the use of a computerized job-exposure matrix (JEM), exposure levels were assigned to each subject for each of 5 known and 2 likely lung carcinogens. A multiple logistic regression model was used to compute the odds ratio (OR) for exposure to each carcinogen, adjusted for age, ethnicity, and pack-years of smoking. On the basis of the criterion of either a dose-response effect or a statistically significant OR (P less than .05) or both, 5 of the 7 carcinogens (4 of the 5 known carcinogens) were found to be associated with lung cancer risk. However, on the basis of the single criterion of a significant OR, only 3 of the 7 carcinogens (2 of the 5 known carcinogens) were associated with lung cancer risk. Due to its relative insensitivity, this JEM may have limited usefulness in the identification of exposure-disease relationships and should not be applied uncritically.

Vegetable consumption and lung cancer risk: a population-based case-control study in Hawaii.

We conducted a population-based study of diet and lung cancer among the multiethnic population of Hawaii in 1983-1985. We completed interviews for 230 men and 102 women with lung cancer and 597 men and 268 women controls, frequency-matched to the patients by age and sex. A quantitative dietary history assessed the usual intake of foods rich in vitamins A and C and carotenoids. A clear dose-dependent negative association was demonstrated between dietary beta-carotene and lung cancer risk in both sexes. After adjusting for smoking and other covariates, the men in the lowest quartile of beta-carotene intake had an odds ratio of 1.9 (95% confidence interval, 1.1-3.2) compared to those in the highest quartile of intake. The corresponding odds ratio for women was 2.7 (95% confidence interval, 1.2-6.1). No clear association was found for retinol, vitamin C, folic acid, iron, dietary fiber, or fruits. All vegetables, dark green vegetables, cruciferous vegetables, and tomatoes showed stronger inverse associations with risk than beta-carotene. This observation suggests that other constituents of vegetables, such as lutein, lycopene, and indoles, and others, may also protect against lung cancer in humans.

An epidemiologic study on the association between diet and breast cancer.

A case-control study of breast cancer was conducted in Hawaii with Japanese and Caucasian women between ages 45 and 74. Each case was matched to one hospital and one neighborhood control. In all, 183 sets of Japanese and 161 sets of Caucasian subjects were interviewed. No statistically significant differences were found between cases and controls in their mean intake of total fat, saturated fat, oleic acid, linoleic acid, animal protein, and cholesterol. Although there was a suggestion that cases consumed more saturated fat and oleic acid than neighborhood controls, the differences were not impressive. Consistent with other case-control studies, the present investigation did not provide strong support for the hypothesis that a high-fat diet is a risk factor for breast cancer. Further work is suggested to clarify the role of diet in determining breast cancer risk.

Intake of flavonoids and lung cancer.

BACKGROUND: To investigate the possible relationship between intake of flavonoids-powerful dietary antioxidants that may also inhibit P450 enzymes-and lung cancer risk, we conducted a population-based, case-control study in Hawaii. METHODS: An in-person interview assessed smoking history and usual intake of 242 food items for 582 patients with incident lung cancer and 582 age-, sex-, and ethnicity-matched control subjects. Subjects who donated a blood sample were genotyped for the P450 enzyme variant allele CYP1A1*2 by use of a polymerase chain reaction-based method. Logistic regression analysis was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). All P values are two-sided. RESULTS: After adjusting for smoking and intakes of saturated fat and beta-carotene, we found statistically significant inverse associations between lung cancer risk and the main food sources of the flavonoids quercetin (onions and apples) and naringin (white grapefruit). The lung cancer OR for the highest compared with the lowest quartile of intake was 0.5 (95% CI = 0.3-0.9) for onions (P for trend =.001) and 0.6 (95% CI = 0.4-1.0) for apples (P for trend =.03). The OR for the highest compared with the lowest tertile of intake for white grapefruit was 0.5 (95% CI = 0.2-0.9) (P for trend =.02). No association was found for important food sources of other flavonoids. Using published food-composition data for flavonoids, we found an inverse association between intake of quercetin and risk of lung cancer (P for trend =.07) that appears consistent with associations for its food sources. The effect of onions was particularly strong against squamous cell carcinoma (a cell type specifically associated with CYP1A1*2 in our study) and was modified by the CYP1A1 genotype, suggesting that CYP1A1 may play a role in this association. CONCLUSION: If replicated, particularly in prospective studies, these findings would suggest that foods rich in certain flavonoids may protect against certain forms of lung cancer and that decreased bioactivation of carcinogens by inhibition of CYP1A1 should be explored as underlying mechanisms.

Cancer mortality in a cohort of naval shipyard workers in Hawaii: early findings.

A retrospective cohort study was performed in Hawaii among 4,779 male shipyard workers exposed to asbestos and 2,757 similar male workers without known asbestos exposure. Observed deaths from cancer and other causes in the 2 groups were compared with expected deaths on the basis of the general population of Hawaii by the use of a modified life-table method of analysis. A risk ratio for lung cancer of 1.7 was found for the exposed group after 20 or more years of follow-up. No increased risk for lung cancer was seen in the nonexposed group. These findings could not be attributed to differences in smoking habits in the 2 shipyard groups or between the shipyard groups and the general population. Because the maximum duration of follow-up for this analysis was 24 years, greater risks for lung cancer may be seen in the exposed group when the follow-up period is extended.

Smoking history and lung cancer survival in women.

The 12-month survival of 223 women with primary lung cancer was examined according to their smoking status given in the hospital record. A multivariate regression model was used to adjust simultaneously for age, tumor stage at diagnosis, tumor histology, and treatment. With adjustment for all these covariates, the 136 ever-smokers demonstrated a significantly greater probability of dying during the 12 months after diagnosis than the 87 never-smokers (odds ratio = 1.74; P = 0.023).